Tumor Cysteine Proteinases, Platelet Aggregation and Metastasis

Abstract

Cysteine proteinases are a subclass of endopeptidases which require activation by thiol reagents (1). This group of enzymes includes the plant proteinase papain, the lysosomal cysteine proteinases (cathepsins B, H and L) and the cytosolic calcium-activated neutral proteinases (CANP). Sequence homologies among the cysteine proteinases suggest that they may have a common evolutionary origin. Takio et al. (2) compared the amino acid sequences of papain and of rat liver cathepsins B and H and found substantial sequence homologies among the three. Surrounding the active site cysteine, cathepsin B has 10 of 11 and cathepsin H 9 of 11 amino acids found in papain. Overall, however, cathepsin H is more closely homologous to papain than to cathepsin B. A peptide containing the active site cysteine residue of chicken skeletal muscle CANP was isolated and found to consist of 7 residues of which 3 are common to the active sites of papain and cathepsin B (3) and cathepsin H (2). Bajkowski and Frankfater (4, 5) have provided evidence that there are functional homologies as well as structural homologies between the active sites of cathepsin B and papain.